Cancer is one of the most serious diseases in man and the second most fatal disease, after atherosclerosis. Breast cancer is the most common cancer among African American women, Recently, interest in herbal extracts for the prevention and treatment of this disease has increased, for such extracts are considered to be safe, economically feasible, and effective. Withania somnifera (WS), commonly known as ashwagandha, has been used for many years in traditional medicine, especially in the treatment of human tumors, arthritis, and stress. This small, woody shrub, which grows about two feet in height, is found in Africa, the Mediterranean, India, and the United States, where it is known as winter cherry. Preliminary data from our laboratory, obtained on a previous pilot project, funded by the MSM/TU/UAB CCC Partnership, show that daily administration of a root extract of WS (given as an oral dose of 300 mg/kg for 21 days) causes 99% grov\rth inhibition of breast cancer cells xenografted in mice. The main goal of this proposal is to determine a safe and efficacious dose of WS for use in rats for chemoprevention in methylnitrosourea (MNU)-induced mammary tumors and in mice for therapy of xenografted breast cancer cells. In addition, the effect of the WS root extract, alone and in combination with tamoxifen, will be evaluated in a panel of breast cancer cell lines in vitro. The molecular effects of WS extract will be evaluated by using slices of tumors obtained from treated animals and breast cancer cells exposed to the extract.